Pathological Conversion of Mouse Perivascular Adipose Tissue by Notch Activation
Joshua M Boucher1, Larisa Ryzhova1, Anne Harrington1
1From the Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough.
Arteriosclerosis, Thrombosis, and Vascular Biology
|July 10, 2020
Summary
Perivascular adipose tissue (PVAT) undergoes pathological changes during obesity, losing its protective effects. Increased Notch signaling in PVAT drives lipid accumulation and inflammation, contributing to vascular disease.
Area of Science:
- Vascular biology
- Adipose tissue biology
- Molecular mechanisms of obesity
Background:
- Perivascular adipose tissue (PVAT) is crucial for vascular health.
- Obesity impairs PVAT's vasoprotective functions through molecular and cellular changes.
- Understanding PVAT's pathological conversion is key to addressing obesity-related vascular dysfunction.
Purpose of the Study:
- To investigate the molecular and functional changes in PVAT during obesity.
- To identify novel markers and pathways involved in PVAT's pathological conversion.
- To elucidate the role of Notch signaling in PVAT dysfunction.
Main Methods:
- Proteomic analysis of PVAT from mice on high-fat or calorie-restricted diets.
- Investigated markers of thermogenic adipocytes and 'whitening' pathways.
- Utilized genetic manipulation (Adipoq-Cre) to activate/inhibit Notch signaling in adipocytes.
- Characterized PVAT-derived preadipocytes.
Main Results:
- PVAT exhibits a unique protein signature distinct from other adipose depots.
- High-fat diet induced a 'whitening' phenotype in PVAT, suppressing UCP1 and increasing lipid deposition, leptin, and inflammation.
- Elevated Notch signaling in PVAT mimicked high-fat diet effects, promoting adipogenesis and lipid accumulation.
- Calorie restriction decreased Notch signaling and lipid content in PVAT.
- PVAT preadipocytes have distinct surface marker expression compared to other depots.
Conclusions:
- PVAT's unique protein signature is modulated by dietary stress.
- Increased Notch signaling in PVAT is sufficient to trigger pathological conversion, promoting lipid accumulation.
- This PVAT conversion may predispose the vascular microenvironment to disease.
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